GFCF-ref-8

Gluten and Autism Spectrum Disorder

Authors:
Croall, I.D., Hoggard, N. and Hadjivassiliou, M.

Higher Prevalence: Individuals with autism experience significantly higher rates of GI symptoms compared to typically developing (TD) children.

Evidence:
- A 2014 study by Chaidez et al. reported odds ratios (OR) ranging from 3.14 (abdominal pain) to 8.61 (food sensitivity) for GI issues in children with ASD (Austism spectrum disorder).
- A 2014 meta-analysis confirmed increased prevalence of general GI concerns (OR 4.42), diarrhea (OR 3.63), constipation (OR 3.86), and abdominal pain (OR 2.45) in ASD.

Significant Association: Large epidemiological studies, particularly from Sweden, indicate a modest comorbidity between ASD and CD.
- A 2017 study reported a hazard ratio (HR) of 1.5 for developing ASD after a childhood CD diagnosis.
- A meta-analysis found an OR of 1.53 for CD patients having ASD.
Reverse Association: Studies exploring whether ASD increases CD risk are less conclusive, though some suggest an increased presence of CD serological markers (e.g., anti-gliadin antibodies [AGA]) without full CD, hinting at broader gluten sensitivity in ASD.

Potential Pathways: Several theories explain how gluten might influence ASD symptoms:
- Autoimmunity: Heightened autoimmunity in ASD may allow gluten to trigger immune responses that worsen symptoms.
- Opioid Activity: Improperly digested gluten peptides (exorphins) could stimulate opioid receptors, potentially affecting social behavior.
- Oxidative Stress: Both ASD and gluten sensitivity are linked to increased oxidative stress, possibly causing brain inflammation.
- Shared Genetics: Certain HLA haplotypes (e.g., HLA-DRB111-DQB107) are more common in both ASD and CD, suggesting a genetic overlap.
Antibodies: Elevated levels of gluten-related antibodies (e.g., AGA, TG6) are reported in some ASD studies, though findings are inconsistent.

Early Trials: Studies from the 1990s and 2000s suggested potential benefits of GFD or gluten- and casein-free diets (GCFD) on ASD symptoms, but were limited by small samples and poor design.
Recent RCTs: Randomized controlled trials (RCTs) show mixed results:
- Some report improvements in behavioral and intellectual outcomes (e.g., communication, social interaction).
- Others find no significant effects.
Limitations: Trials suffer from heterogeneity in design, small sample sizes, short durations, and lack of blinding, preventing definitive conclusions.

High Usage: Despite inconclusive evidence, 10% to over 50% of individuals with ASD adopt GFD (Gluten free diet) or GCFD(Gluten free casien free diet).
Anecdotal Reports: Parents frequently report symptom improvements, though statistical evidence is inconsistent.
Motivations: Adoption is driven by anticipated regret, perceived control, and recommendations from medical or community sources.

Mixed Impact: Limited studies suggest:
- Benefits: Higher intake of vitamins D and E, magnesium, and better bone health markers in some cases, often linked to supplement use.
- Risks: Potential deficiencies, such as lower tryptophan levels, which might worsen ASD symptoms.
Need for Balance: A balanced diet is crucial when following restricted regimens.

Key Insights: There is evidence of a modest ASD-CD comorbidity and plausible mechanisms for gluten’s effects, but trial data is insufficient to support GFD as a standard ASD treatment.
Research Gaps:
- Need for well-powered, long-duration, placebo-controlled RCTs with standardized outcomes.
- More studies on adults with ASD, as current research focuses heavily on children.
- Further investigation into genetic and physiological links.